Monocyte-mediated Serum-independent Damage to Hyphal and Pseudohyphal Forms of Candida albicans In Vitro

Abstract

A B S T R A C T Human peripheral blood monocytes attached to Candida albicans hyphae in the absence of serum and damaged the hyphae without completely ingesting them. Attachment and damage was not augmented by the addition of serum. Damage to hyphae was quantitated by a previously developed metabolic assay that measured leukocyte-induced reduction in uptake of [14C]cytosine by the hyphae. Use of cells from patients with hereditary disorders of leukocyte function, chronic granulomatous disease, and myeloperoxidase deficiency indicated that myeloperoxidaseindependent and nonoxidative mechanisms could sometimes damage hyphae where oxidative mechanisms were impaired. Damage to hyphae by normal monocytes was inhibited by concentrations of sodium azide and sodium cyanide that primarily affect myeloperoxidase activity, as well as by halide-free conditions, catalase, and putative antagonists of hypochlorous acid or singlet oxygen. Iodination ofhyphae, a myeloperoxidase and hydrogen peroxide-dependent process of monocytes, was similarly inhibited by sodium azide, sodium cyanide, and catalase. Under anaerobic conditions, damage to hyphae was reduced by 64.0-68.4%. In contrast, inhibitors ofpotential nonoxidative antifungal mechanisms, iron salts to saturate iron chelators, and polyanionic amino acid polymers to neutralize cationic proteins did not block damage to hyphae by monocytes. Preparations rich in lysosomal granules from fractionated normal monocytes also did not damage hyphae. Overall, it appeared that oxidative mechanisms were most important for damage to hyphae by normal monocytes.Dr.

Candida albicansIs Phagocytosed, Killed, and Processed for Antigen Presentation by Human Dendritic Cells

“…In contrast, murine FSDC do produce NO upon phagocytosis of Candida and hyphae, but no definitive evidence was presented to demonstrate that NO actually was responsible for killing the Candida cells (19). As our immature DC were derived from peripheral blood monocytes, these data fit in with the general idea that the preponderance of human neutrophil candidacidal activity is mediated via the production of toxic oxygen metabolites (16,77,81), whereas killing of Candida by human monocytes and M occurs predominantly though nonoxidative mechanisms (17,44,77).…”

Fungicidal activity of Candida albicans-induced murine lymphokine-activated killer cells against C. albicans hyphae in vitro

“…These authors have shown that significant anti-hyphal activity is exerted by lymph node cells pre-exposed in vitro to IL-2 and conclude that the active effector cell is functionally and phenotypically similar to an activated NK cell. While previous reports (Diamond et al, 1978(Diamond et al, , 1981Baccarini et al, 1985;Scaringi et al, 1991) have shown that hyphae can be damaged by PMN cells and monocytes, our data together with those of Beno & Mathews (1 990) indicate that non-phagocytic effector cells can also exert anti-hyphal activity.…”

Monocyte and granulocyte-mediated tumor cell destruction. A role for the hydrogen peroxide-myeloperoxidase-chloride system.

“…Indeed, MPO-deficient granulocytes successfully destroyed both erythrocyte3 and endothelial cell targets (23). Recent reports have also demonstrated that human monocytes and neutrophils can destroy target cells in antibody dependent (14,(50)(51)(52) or serum independent systems (53 …”